12-132685415-C-T

Position:

• chr12-132685415-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006231.4(POLE):​c.62+1839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,172 control chromosomes in the GnomAD database, including 32,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (32156 hom., cov: 34)
• Consequence: POLE NM_006231.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

Genes affected

POLE (HGNC:9177): (DNA polymerase epsilon, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]

POLE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLE	NM_006231.4	c.62+1839G>A		intron_variant		ENST00000320574.10	NP_006222.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574.10	c.62+1839G>A		intron_variant		1	NM_006231.4	ENSP00000322570.5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97921 AN: 152054 Hom.: 32115 Cov.: 34

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.654

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.644 AC: 98009 AN: 152172 Hom.: 32156 Cov.: 34 AF XY: 0.636 AC XY: 47312 AN XY: 74398

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.652

Alfa AF: 0.673 Hom.: 16299

Bravo AF: 0.640

Asia WGS AF: 0.517 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11147005; hg19: chr12-133262001; COSMIC: COSV57691628; COSMIC: COSV57691628;